title: The role of afferents to the ventral tegmental area in the handling stress-induced increase in the release of dopamine in the medial prefrontal cortex: a dual-probe microdialysis study in the rat brain.
abstract: This study was aimed to identify the neuronal pathways that mediate the handling stress induced increase in the release of dopamine in the medial prefrontal cortex (mPFC) of the rat brain. For that purpose a microdialysis probe was implanted in the ventral tegmental area (VTA) and a second probe was placed in the ipsilateral mPFC. Receptor specific compounds acting on GABA(A) (20 microM muscimol), GABA(B) (50 microM baclofen), acetylcholine (100 microM atropine, 100 microM mecamylamine), NMDA (30, 100 and 300 microM CPP; 300 microM AP-5, 1 mM (+)-HA-966) and non-NMDA receptors (500 microM CNQX) were infused into the VTA by retrograde dialysis, whereas extracellular dopamine was recorded in the ipsilateral mPFC. Intrategmental infusion of muscimol, baclofen, CPP, AP-5, (+)-HA-966 and CNQX decreased extracellular dopamine in the ipsilateral mPFC; atropine and mecamylamine were without effect on the basal values. During infusion of the various compounds rats were gently handled for 15 min. The infusions of muscimol, atropine, mecamylamine and (+)-HA-966 did not modify the handling stress induced increase in extracellular dopamine in the mPFC. However, during intrategmental infusion of baclofen, CPP, AP-5 and CNQX the handling stress induced increase in extracellular dopamine (expressed as % of controls) in the mPFC was suppressed. These results indicate that a glutamatergic projection to the VTA, acting via both NMDA and non-NMDA-glutamate receptors, play a major role in the handling stress-induced increase in dopamine release in the mPFC. In addition the results suggest a certain role for GABAergic neurones, acting via GABA(B) receptors, in the handling response.
authors.affiliation: Institute of Pharmacology, University of Sassari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Enrico
authors.forename: M
authors.initials: M
authors.lastname: Bouma
authors.forename: J B
authors.initials: JB
authors.lastname: de Vries
authors.forename: B H
authors.initials: BH
authors.lastname: Westerink
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006234:Handling, Psychological; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D017551:Microdialysis / Q000379:methods; D009118:Muscimol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000187:drug effects; D018079:Receptors, GABA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000502:physiology*
chemical_list: D011950:Receptors, Cholinergic; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D009118:Muscimol; D008464:Mecamylamine; D001418:Baclofen; D004298:Dopamine